title: Vitamin C inhibits p53-induced replicative senescence through suppression of ROS production and p38 MAPK activity.
abstract: We previously reported that tumor cells expressing p53 increase intracellular levels of reactive oxygen species (ROS). In this study, we described an inhibitory effect of vitamin C on replicative senescence. Vitamin C was found to inhibit p53-induced senescence in human bladder cancer EJ cells. The senescence-like phenotype (SLP) induced by p53, which showed a morphological change and an irreversible cell cycle arrest, was not observed in vitamin C-treated EJ cells. In addition, vitamin C did not significantly affect normal cell proliferation. We investigated the molecular mechanisms of the inhibitory effect of vitamin C on the development of replicative senescence in EJ cells. We found that vitamin C inhibited this p53-induced ROS generation. Moreover, p38 kinase which was activated during p53-induced senescence was not observed in vitamin C-treated EJ cells. SB203580, a chemical inhibitor of p38 kinase, was found to consistently inhibit p53-induced senescence. Therefore, it is suggested that vitamin C inhibits p53-induced senescence by preventing ROS generation, which in turn leads to the activation of p38 MAPKinase. These results reveal the inhibitory mechanism of vitamin C on cellular senescence.
authors.affiliation: Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine, Jongno-Gu, Seoul, Korea.
authors.forename: Jee-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Jin
authors.forename: Soon-Duck
authors.initials: SD
authors.lastname: Lee
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Hong
authors.forename: Jae-Sik
authors.initials: JS
authors.lastname: Shin
authors.forename: Seung-Koo
authors.initials: SK
authors.lastname: Lee
authors.forename: Da-Jung
authors.initials: DJ
authors.lastname: Jung
authors.forename: Jae-Seung
authors.initials: JS
authors.lastname: Kang
authors.forename: Wang-Jae
authors.initials: WJ
authors.lastname: Lee
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D001205:Ascorbic Acid